Zika Virus Infects Human Placental Macrophages

Kendra M. Quicke, James R. Bowen, Erica L. Johnson, Raymond F. Schinazi,Rana Chakraborty, Mehul S. Suthar

Cell Host Microbe. (2016) 20(1):83-90

Speaker: Martyr Yang（楊俊常）                                       Time: 16:00~17:00, Oct. 26, 2016

Commentator: Dr. Guey-Chuen Perng (彭貴春教授)          Place: Room 601

Abstract:

Zika virus (ZIKV) is a positive-sense RNA virus which belongs to the Flaviviridae family that spread mostly by the Aedes species mosquito. From 1 January 2007 to 29 September 2016, ZIKV transmission was documented in a total of 73 countries and territories. ^[1] ZIKV causes diseasewith symptoms including mild fever, conjunctivitis, skin rash, muscle and joint pain, malaise or headache. In infected mother, ZIKV can be vertically transmitted to fetus resulting in fetal brain abnormalities and microcephaly. However, the mechanism of intrauterine transmission and the cell types involved remain unclear. Usually, the placenta acts as a physical barrier between the maternal and fetal chorionic villi to protect the developing fetus from the vertical transmission of viruses. Each villus is lined by trophoblasts (cytotrophoblasts [CTBs] and syncytiotrophoblasts [STBs]), which encase the fetal blood supply and primary human placental macrophages (Hofbauer cells [HCs]). Nevertheless, ZIKV antigen and RNA was found in the chronic villi of a human placenta from a mother who gave birth to an infant with microcephaly recently. Furthermore, a study showed that syncytiotrophoblasts (differentiated cytotrophoblasts) appear to be resistant to infection by historic ZIKV strains at early time infection (24 and 48 hr post-infection). ^[2] In this study, term (>37 weeks gestation) placentae from HIV-1 seronegative and hepatitis B-uninfected women (>18 years of age) were obtained immediately following elective cesarean section without labor for experimental purpose. The authors demonstrate that the contemporary ZIKV strain PRVABC59 (PR 2015) infects and replicates in HCs, and to a lesser extent in CTBs, isolated from villous tissue of full-term placentae. Furthermore, ZIKV infection induces activation of HCs and production of IFN-α and other pro-inflammatory cytokines. Analysis of antiviral gene expression shows upregulation of retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) transcription as well as downstream effector genes in HCs and CTBs. Overall, these results suggest a mechanism for intrauterine transmission of ZIKV gains access to the fetal compartment by infecting and proliferating in human placental macrophages.

References:

1) WHO. (2016) Situation report : Zika virus microcephaly and guillain-barré syndrome.

2) Bayer, A., et al. (2016). Type III interferons produced by human placental trophoblasts confer protection against Zika virus infection. Cell Host Microbe 19, 705–712.